Lindsay E. Calderon
The effects of iPLA2β (Ca2+-independent Phospholipase A2β) and MMP-9 (Matrix Metalloproteinase-9) on the migration of cancer cells have been a recent focus for biomedical research and have been found to be over-expressed. However, their roles are not entirely known, especially concerning nicotine-induced breast cancer cell advancement, which has not been thoroughly investigated. The purpose of this study is to determine the involvement of iPLA2β in nicotine-induced breast cancer cell advancement. BEL (bromoenol lactone), a suicide inhibitor of iPLA2β, was hypothesized to decrease the intensity of the effects of nicotine-induced breast cancer. Following the BEL treatment, the in-vitro results exhibited a significant debilitation of 4T1 cell proliferation for both basal and nicotine-induced, as shown in the MTT proliferation assay. Scratch and transwell assays revealed migration was also negatively affected. The expression of MMP-9 was discovered to have behaved in an iPLA2β-dependent manner, which further supports the idea that iPLA2β plays a significant role, concerning the mediation of basal and nicotine-induced cancer cell progression. In-vivo results also supported this conclusion. In mice, basal and nicotine-induced tumor growth was significantly decreased, in comparison with the control group. BEL also reduced nicotine-induced HIF-1alpha, CD31, and MMP-9 tumor expression, as shown by the immunohistochemical analysis; the presence of nicotine-induced tumors in lung tissue was reduced significantly. In-vitro and in-vivo results suggest that MMP-9 behaves in an iPLA2β-dependent manner and consequently mediates nicotine-induced breast cancer cell migration and proliferation. Because BEL was found to reduce the effects of this, it may be a possible chemotherapeutic drug.